Last updated:
April 1, 2026
Neonatal sepsis is a life-threatening bloodstream infection that affects infants < 28 days old.
Definition of terms
| Term | Definition |
|---|---|
| Suspected sepsis | Presence of sepsis risk factors in the baby, or findings suggesting sepsis regardless of whether there are symptoms or not. |
| Clinical sepsis | Clinical features and lab findings are present, but fail to show causative organisms |
| Proven sepsis | Clinical features and lab findings are present, and demonstrated organisms in cultures taken from a sterile field |
| Sepsis criteria | SIRS + source of infection (suspected or present) |
| Severe sepsis | Sepsis with acute organ dysfunction (including hypoperfusion and hypotension) caused by sepsis |
| Septic shock | Sepsis with persistent or refractory tissue hypoperfusion or hypotension despite adequate fluid resuscitation |
SIRS criteria (≥ 2 required, 1 must be abnormal temperature or leukocyte count)
- Temperature > 38.5 C or < 36 C
- Abnormal leucocyte count OR > 10% band
- Tachycardia, or Bradycardia (if < 1 year)
- Tachypnea, or Mechanical ventilation (related to an acute process)
Early onset vs. late onset neonatal sepsis
| Early-onset sepsis (EOS) | Late-onset sepsis (LOS) | |
|---|---|---|
| Time of onset | ≤ 72 hours | ≥ 72 hours |
| Source of infection | Antenatal (maternal) genitourinary tract | Post-natal environment (healthcare workers, caregivers) |
| Presentation | Pneumonia (respiratory distress) is the most common, fulminant multisystem | Meningitis is frequent, slowly progressive |
| Causative organisms | Group B streptococci, Escherichia coli (common in preterm), CoNS (Staphylococcus epidermidis), Haemophilus influenzae, Listeria monocytogenes | CoNS (> 50%), Staphylococcus aureus, Haemophilus influenzae, Klebsiella, Pseudomonas, Viruses, Candida |
Risk factors for early-onset sepsis
| Category | Risk factors |
|---|---|
| Maternal factors | Prolonged rupture of membranes > 18 hours, Intrapartum maternal fever (> 38 C), Chorioamnionitis, UTI, GBS colonization, Foul-smelling and/or meconium-stained liquor, single unclean or > 3 sterile vaginal examinations during labour |
| Fetal factors | Prematurity, low birth weight, difficult delivery, e.g., prolonged 1st and 2nd stage of labour > 24 hours, perinatal asphyxia (APGAR < 4 at 1 minute) |
Risk factors for late-onset sepsis
| Category | Risk factors |
|---|---|
| Hospitalization | ICU admission and instrumentation (umbilical catheter, endotracheal intubation, IV catheter) |
| Congenital malformation | Spina bifida, tracheo-esophageal fistula, and congenital heart disease |
| Sever illness | Immunodeficiency, Malnutrition |
Note: Premature and LBW neonates are more susceptible to both EOS and LOS due to:
- Deficient immunity (IgG, opsonization, complement)
- Immature epithelial barrier
- Increased need for invasive devices (vascular access, endotracheal tube, feeding tubes, urinary tract catheters)
Classification of neonatal sepsis according to severity
| Classification | Features |
|---|---|
| Non-severe neonatal sepsis | Movement only when stimulated, not feeding well on observation, temperature > 37 C or < 35.5 C, severe chest wall indrawing |
| Severe neonatal sepsis | Unconscious, convulsions, unable to feed or poor feeding, apnoea, unable to cry/high-pitched cry, central cyanosis (SpO2 <90% or requiring oxygen), bulging fontanelles, persistent vomiting |
Clinical presentation of neonatal sepsis
| Category | Signs and symptoms |
|---|---|
| Early | Irritability, respiratory distress with apnoeic attacks, lethargy, poor feeding, vomiting, unstable temperature (fever or hypothermia), poor moro and sucking reflexes |
| Respiratory | Fast breathing, difficulty in breathing (expiratory grunting), Nasal flaring and intercostal/sternal retractions, apnoea (common in preterms), cyanosis (SpO2 < 90%) |
| CNS | Difficulty sucking, irritability, lethargy, sleepiness, weak or high-pitched cry, convulsions, hypoactivity, hypotonic, bulging or tense fontanelles, body temperature regulation problems (hypothermia or hyperthermia) |
| Cardiovascular | Bradycardia or tachycardia, hypotension, prolonged capillary refill time (> 3 seconds since blood is redistributed to maintain flow to the heart and brain) |
| Gastrointestinal | Vomiting, difficulty sucking, diarrhea, abdominal distension, hepatosplenomegaly, jaundice |
| Dermatological | Jaundice, cyanosis, cutis marmorata, pustules, abcess, petechiae, purpura, neonatal sclerema (hardening of the skin), skin mottling |
- Differentials
- Congenital heart disease
- Neonatal encephalopathy
- Metabolic disease
- Prematurity and other associated complications
- NRDS
- Intraventricular hemorrhage
- Apnoea of prematurity
- Hypothyroidism or hyperthyroidism
- Transient Tachypnoea of the Newborn
- Meconium aspiration syndrome
- Hypoglycemia
- Investigations
- Blood culture: This is the gold standard.
- A negative blood culture does not exclude diagnosis ****
- Complete blood count with Immature: total (I: T) ratio:
- I: T ratio of > 0.18
- Neutropenia/neutrophilia
- Thrombocytopenia
- Neutropenia has better specificity than neutrophilia as a marker of neonatal sepsis
- CRP
- Elevated (low sensitivity for EOS)
- Procalcitonin
- Elevated (higher sensitivity for EOS than CRP)
- CSF culture: This is done in infants with positive blood culture and clinically considered meningitis. It is routinely performed in small children with late-onset sepsis.
- CSF biochemical analysis
- Urinalysis and urine culture: no need in EOS, but used in LOS
- Chest X-ray: used in cases with respiratory symptoms to rule out pneumonia.
- Cell surface markers
- Blood culture: This is the gold standard.
- Supportive Treatment
- Early transfer to the NICU for a critically ill neonate requiring cardiopulmonary support
- Encourage breastfeeding, nasogastric tube feeds, or **intravenous fluids if feeding is not feasible
- Monitor input/output charts
- Transfusion of blood products if indicated
- Oxygen therapy
- If respiratory compromise or SpO2 < 90%
- Keep warm if the temperature is < 35.5 C
- Expose if the temperature is ≥ 38 C
- Encourage KMC
- Check for and prevent hypoglycemia (RBS)
- Treat hypoglycemia if it cannot be tested for in severe neonatal sepsis
- Definitive Treatment of Early-Onset Neonatal Sepsis
- Penicillin/ampicillin + gentamicin
- First-line
- Targets GBS and L. monocytogenes
- Gentamicin protects the penicillin against resistance.
- 3rd and 4th generation cephalosporin, e.g. cefotaxime, if there is suspected Gram-negative meningitis
- Ceftriaxone is not used since it can lead to hyperbilirubinemia and the serious precipitation of calcium-ceftriaxone crystals.
- Metronidazole if there is suspected necrotizing enterocolitis
- Penicillin/ampicillin + gentamicin
- Definitive Treatment of Late-Onset Neonatal Sepsis
- Flucloxacillin and Aminoglycoside
- Targets Staphylcoccus aureus and gram-negative organisms.
- Used if there is suspected staphylococcal septicemia, or neonates have signs of sepsis with skin pustules/abscesses or omphalitis
- Vancomycin
- Targets CoNS
- 3rd gen cephalosporin, e.g. cefotaxime
- If suspected GN meningitis
- Meropenem
- If the patient was previously on a 3rd-generation cephalosporin, or if there is local resistance
- Flucloxacillin and Aminoglycoside
- Preventin
- Intrapartum prophylaxis for GBS-positive mothers
- Limit the number of vaginal examinations and clean aseptic deliveries
- Strict hygiene protocols in the NBU or NICU
- Exclusive breastfeeding if possible
- Maintain a clean and dry cord and isolate infectious babies
Duration of treatment
| Condition | Duration of Treatment |
|---|---|
| Breastfeeding well | 2 days, PO treatment to complete 5 days |
| Skin infection | 3 days, PO treatment to complete 5 days |
| Clinical or radiological Pneumonia | Minimum of 5 days |
| Severe neonatal sepsis | Minimum of 7 days |
| GN bacteremia | 10 – 14 days |
| < 32/40 gestational age | 10 – 14 days |
| Uncomplicated GBS meningitis | minimum 14 days, extend duration if focal complications |
| GN bacterial meningitis | minimum 21 days, or for another 2 weeks after the first negative CSF culture |
Newborn antibiotic doses for neonates < 7 days
| Antibiotic | Dose | Frequency | Route |
|---|---|---|---|
| Penicillin (< 7 days | 50,000 IU/kg | 12 hourly | IV/IM |
| Penicillin (> 7 days) | 50,000 IU/kg | 6 hourly | IV/IM |
| Ampicillin/Flucloxacillin | 50mg/kg | 12 hourly | IV/IM |
| Gentamicin (< 2kg) | 3mg/kg | 24 hourly | IV/IM |
| Gentamicin (≥ 2kg) | 5 mg/kg | 24 hourly | IV/IM |
| Ceftriaxone | 50mg/kg | 24 hourly | IV/IM |
| Metronidazole | 7.5 mg/kg | 12 hourly | IM |
| Oral Amoxicillin | 50mg/kg (100mg/kg/day) | 12 hourly | PO |
Gentamicin frequency
| Gestational age | Interval |
|---|---|
| < 30 0 weeks | 48 hourly |
| 30 0 – 34 6/7 weeks | 36 hourly |
| ≥ 35 + 0 weeks | 24 hourly |